A method and assay for screening panel of prebiotic products to identify the most suitable product for prevention and/or treatment of a specific disorder that is associated with poor gut health is described. Poor gut health can be broadly defined as gut leakiness and/or dysbiosis and/or inflammation and/or other specific indications in a given subject that can be managed, in part, through the use of a prebiotic. Based on the indication, the method provides the opportunity to personalize a prebiotic formulation for use to manage, control or alleviate poor gut heath. The screening assay allows for identifying the appropriate prebiotic or a combination of prebiotics for an individual patient with intestinal and systemic diseases where gut initiated inflammation, dysbiosis [abnormal intestinal microbiota composition] and gut leakiness are key for initiation and/or progression of the disease. Appropriateness of the prebiotic is based on the effects of the prebiotic on the intestinal microbiota composition and fermentation products to promote gut health that may be defined by improved intestinal barrier-less gut leakiness and increased number of probiotic bacteria/less pathogenic bacteria and increased amount of short chain fatty acids like butyrate as well as blunted inflammatory response that may be defined by less production of pro-inflammatory cytokines by their PBMC.
Recent studies have shown that abnormal microbiota composition [dysbiosis] are linked to many intestinal and systemic inflammatory disorders, including food allergy, chronic inflammatory bowel disease (IBD) (i.e. ulcerative colitis and Crohn's disease), HIV, irritable bowel syndrome, diverticular diseases, Clostridium Difficile colitis, alcoholic liver disease, non-alcoholic steatohepatitis (NASH), and even metabolic syndrome and obesity, and neurological disorders like Parkinson's disease, autism and Alzheimer's disease. Furthermore, it is now well established that intestinal microbiota regulate intestinal epithelial barrier function and therefore changes in intestinal microbiota composition not only can promote local and systemic inflammation by producing excessive amounts of pro-inflammatory factors like endotoxins but also can compromise intestinal barrier function (leaky gut) and increase exposure of intestinal and systemic immune systems to these pro-inflammatory factors causing sustained and inappropriate inflammatory response that could lead to above mentioned inflammatory diseases. Thus, intervention to correct dysbiotic intestinal microbiota composition and improve intestinal barrier function could prevent and/or treat these disorders.
Prebiotics are capable of changing microbiota composition and promoting intestinal barrier integrity. Prebiotics are poorly absorbed carbohydrates that can reach into the colon after ingestion and are used by intestinal bacteria as a source of energy for growth. Thus, depending on the type of prebiotic product, the prebiotic product can favor or disfavor growth of specific groups of bacteria and thus are capable of changing the composition of the intestinal microbiota community and promoting health. Prebiotics have been investigated for their capacity to prevent and/or treat intestinal and systemic inflammation in both murine and human studies and their beneficial and anti-inflammatory effects have been established. For example, it has also been shown that the genomic DNA of these bacterial species can promote immunological tolerance. In addition, prebiotic oligosaccharides are fermented by specific bacterial strains present in the gut microbiota, resulting in the production of the short-chain fatty acids (SCFA) acetate, propionate and butyrate that support the barrier function of the intestinal epithelium. Indeed, supplementation of prebiotics into the diet is known to affect the gut microbiota composition. Prebiotics can favor the growth of specific bacterial strains, including Bifidobacteria spp, Lactobacilli and butyrate producing bacteria. The growth of these bacteria promotes immune tolerance and restoration of intestinal barrier integrity presumably through increased production of SCFA.
The challenge in clinical medicine is to determine the type of prebiotic product that is most suitable for a given patient or a group of patients with a specific disease because: (1) not all prebiotics are the same and the effects of the prebiotics on intestinal microbiota composition and fermentation profile is specific for a given product. Furthermore, the impact of a given prebiotic on microbiota composition, immune response and intestinal barrier integrity is highly variable among different subjects; (2) not all individual respond to a given prebiotic similarly; (3) microbiota composition is different among patients even in those with a similar disease and (4) the desired outcome from prebiotic supplementation differs and is based on pathogenesis of a given disease. For example, for some disorders promotion of immune tolerance is the priority, by way of non-limiting example, in the case of a food allergy. In others disorders, restoration of intestinal barrier integrity is the desired outcome, for example in Alzheimer's disease, Parkinson's disease and NASH. Further, in other disorders, restoration of intestinal barrier function and promotion of anti-inflammatory pathways are the key, such as IBD, but not limited thereto. Thus, a method to identify the prebiotic(s) for a given disease state and a given patient is needed to optimize the use of a prebiotic formulation. The bioassay described herein is in response to this challenge and to the clinically significant unmet need.
There is no currently available method to achieve the goal of identifying the prebiotic(s) based on a patient and a disease. The screening method described herein will respond to this unmet need and provide an opportunity to offer a personalized prebiotic treatment to patients who suffers from disorders where changes in microbiota composition and/or function has therapeutic efficacy.